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PubMed2004

Somatic symptoms and physiologic responses in generalized anxiety disorder and panic disorder: an ambulatory monitor study.

BACKGROUND: Physiologic responses of patients with anxiety disorders to everyday events are poorly understood. OBJECTIVE: To compare self-reports and physiologic recordings in patients with panic disorder (PD), patients with generalized anxiety disorder (GAD), and nonanxious controls during daily activities. DESIGN: Participants underwent four 6-hour recording sessions during daily activities while wearing an ambulatory monitor. Physiologic and subjective data were recorded every 30 minutes and during subject-signaled periods of increased anxiety or tension or panic attack. SETTING: Participants' everyday environment. PARTICIPANTS: Twenty-six patients with PD and 40 with GAD, both without substantial comorbidity, and 24 controls. INTERVENTIONS: Recordings obtained during everyday activities. MAIN OUTCOME MEASURES: Recordings of heart interbeat intervals, skin conductance levels, respirations, motion, and ratings of subjective somatic symptoms and tension or anxiety. RESULTS: Patients with anxiety disorders rated higher on psychic and somatic anxiety symptoms than did controls. Common to both anxiety disorders was diminished autonomic flexibility that manifested itself throughout the day, accompanied by less precise perception of bodily states. The main differences between patients with PD and GAD were a heightened sensitivity to body sensations and more frequent button presses. There also was a trend toward heightened basal arousal in patients with PD, manifesting itself in a faster heart rate throughout the day. CONCLUSIONS: Patients with PD or GAD are more sensitive to bodily changes than nonanxious individuals, and patients with PD are more sensitive than those with GAD. Patients with PD experience more frequent distress than those with GAD and controls, but their physiologic responses are comparable in intensity. The findings suggest that the perception of panic attacks reflects central rather than peripheral responses. The diminished autonomic flexibility observed in both anxiety conditions may result from dysfunctional information processing during heightened anxiety that fails to discriminate between anxiety-related and neutral inputs.

Adult↗
PubMed1987

Oral premedication with clonidine: effects on stress responses during general anaesthesia.

The effect of clonidine (4.5 micrograms kg-1) on haemodynamics and hormonal stress responses was evaluated in 21 female patients undergoing breast surgery. The standardized general anaesthesia included diazepam as premedicant, thiopentone, enflurane, N2O, fentanyl and vecuronium. Venous plasma concentrations of noradrenaline, adrenaline, growth hormone, vasopressin, and cortisol were assayed at various times before, during and after surgery. Clonidine attenuated the sympathoadrenal response; arterial blood pressure and heart rate increases in association with intubation were lower in clonidine-premedicated patients. Noradrenaline levels were lower throughout and 3 h after surgery in the clonidine group (P less than 0.05). Adrenaline levels were lower in this group 2 min after intubation (P less than 0.05). Growth hormone, vasopressin and cortisol plasma levels were increased at the end of and after surgery, with no differences between the groups. In spite of the effect on sympathoadrenal response, clonidine did not have any significant additive anxiolytic effect. Statistically significant differences were not found as to need for postoperative analgesics.

Administration, Oral↗
PubMed2004

Predictors of response in generalized social phobia: effect of age of onset.

Selective serotonin reuptake inhibitors (SSRIs) are the gold standard for the pharmacological treatment of generalized social phobia (GSP). However, little is known about the predictors of response to treatment. Two hundred and four outpatients with GSP were randomized to sertraline (Zoloft) or placebo, for a 20-week double-blind study, with a flexible dose range of sertraline 50 to 200 mg/d. Response was defined as the percentage of patients with a Clinical Global Impression-Improvement scale (CGI-I) of 1 (very much improved) or 2 (much improved). Outcome analyses were conducted using regression models including treatment group as a categorical predictor and study visit as a repeated measure. Dependent measures included Marks Fear Questionnaire (MFQ), Brief Social Phobia Scale (BSPS), CGI-I, and Sheehan Disability Scale (SDS). We investigated several possible predictors of response to treatment including DSM-IV comorbidity, age, sex, age of onset of GSP, and duration of illness. Patients with later-onset (especially adult-onset) GSP tend to have a better response to treatment than those with earlier-onset GSP. This result generally appears in our analyses as a 2-way interaction, where the association with response is greatest for patients with adult-onset GSP (in contrast to those with child or adolescent onset). This finding is most robust for symptom measures, but is still apparent for the Sheehan measure of disability at work. This advantage for later-onset GSP can be accounted for neither by severity of illness nor by duration of illness. Superior treatment outcome for later-onset GSP may be mediated by the degree of social and family disability.

Adolescent↗
PubMed1981

Spinal neurons mediate return of substance P following deafferentation of cat spinal cord.

Deafferentation of the cat dorsal horn by complete unilateral lumbosacral dorsal rhizotomy produces a loss and subsequent partial recovery of substance P (SP) immunoreactivity as visualized by the peroxidase-antiperoxidase technique. The present experiments aimed to determine whether this return of SP represents a generalized response of all fiber systems afferent to the denervated segments or a more selective response of a specific spinal system. Although a contribution from other sources cannot be excluded by this qualitative immunocytochemical technique, several observations indicate that the return of SP staining depends on interneurons which contain SP immunoreactivity: (1) the amount of SP staining in the chronically deafferented dorsal horn deprived of extrinsic fiber systems is comparable to that seen after deafferentation alone; (2) SP-containing neurons are present within the lumbar segments; and (3) destruction of lumbar neurons by the intraspinal injection of kainic acid abolishes SP staining from the chronically deafferented dorsal horn. From these observations it would appear that the anatomical plasticity of SP-containing fibers in the deafferented dorsal horn is due to the response of a particular system rather than to a generalized response of all systems which terminate there.

Afferent Pathways↗
PubMed2003

Response to acetaldehyde stress in the yeast Saccharomyces cerevisiae involves a strain-dependent regulation of several ALD genes and is mediated by the general stress response pathway.

One of the stress conditions that yeast may encounter is the presence of acetaldehyde. In a previous study we identified that, in response to this stress, several HSP genes are induced that are also involved in the response to other forms of stress. Aldehyde dehydrogenases (ALDH) play an important role in yeast acetaldehyde metabolism (e.g. when cells are growing in ethanol). In this work we analyse the expression of the genes encoding these enzymes (ALD) and also the corresponding enzymatic activities under several growth conditions. We investigate three kinds of yeast strains: laboratory strains, strains involved in the alcoholic fermentation stage of wine production and flor yeasts (responsible for the biological ageing of sherry wines). The latter are very important to consider because they grow in media containing high ethanol concentrations, and produce important amounts of acetaldehyde. Under several growth conditions, further addition of acetaldehyde or ethanol in flor yeasts induced the expression of some ALD genes and led to an increase in ALDH activity. This result is consistent with their need to obtain energy from ethanol during biological ageing processes. Our data also suggest that post-transcriptional and/or post-translational mechanisms are involved in regulating the activity of these enzymes. Finally, analyses indicate that the Msn2/4p and Hsf1p transcription factors are necessary for HSP26, ALD2/3 and ALD4 gene expression under acetaldehyde stress, while PKA represses the expression of these genes.

Acetaldehyde↗
PubMed1970

Generalization and response mediation of a conditional discrimination.

Fifteen pigeons were given conditional discrimination training in which a colored sample stimulus determined which of two line comparison stimuli (vertical and horizontal) was correct. As part of the conditional discrimination procedure, birds were required to make an "observing response" to the sample stimulus presented on a wide key. The location on this key of the required observing response for the two sample stimuli differed by 0, 3, or 6 in. (0, 7.6, or 15.2 cm) for three groups of birds. Accuracy of conditional discrimination performance was directly related to the amount of separation. In subsequent generalization tests with novel sample stimuli, both observing-response location and comparison responding changed within the same region of the wavelength continuum from that appropriate for one of the training samples to that appropriate for the other. A maintained generalization test (continued reinforcement for training stimuli) revealed this relation more strongly. A test in which observing-response location was the only sample stimulus of a conditional discrimination revealed stimulus control by this observing response, supporting a response mediation interpretation of the data.

Animals↗
PubMed2001

General stress response of Bacillus subtilis and other bacteria.

One of the strongest and most noticeable responses of a Bacillus subtilis cell to a range of stress and starvation conditions is the dramatic induction of a large number of general stress proteins. The alternative sigma factor sigma B is responsible for the induction of the genes encoding these general stress proteins that occurs following heat, ethanol, salt or acid stress, or during energy depletion. sigma B was detected more than 20 years ago by Richard Losick and William Haldenwang as the first alternative sigma factor of bacteria, but interest in sigma B declined after it was realized that sigma B is not involved in sporulation. It later turned out that sigma B, whose activity itself is tightly controlled, is absolutely required for the induction of this regulon, not only in B. subtilis, but also in other Gram-positive bacteria. These findings may have been responsible for the recent revival of interest in sigma B. This chapter summarizes the current information on this sigma B response including the latest results on the signal transduction pathways, the structure of the regulon and its physiological role. More than 150 general stress proteins/genes belong to this sigma B regulon, which is believed to provide the non-growing cell with a non-specific, multiple and preventive stress resistance. sigma B-dependent stress proteins are involved in non-specific protection against oxidative stress and also protect cells against heat, acid, alkaline or osmotic stress. A cell in the transition from a growing to a non-growing state induced by energy depletion will be equipped with a comprehensive stress resistance machine to protect it against future stress. The protection against oxidative stress may be an essential part of this response. In addition, preloading of cells with sigma B-dependent stress proteins, induced by mild heat or salt stress, will protect cells against a severe, potentially lethal, future stress. Both the specific protection against an acute emerging stress, as well as the non-specific, prospective protection against future stress, are adaptive functions crucial for surviving stress and starvation in nature. We suggest that the sigma B response is one essential component of a survival strategy that ensures survival in a quiescent, vegetative state as an alternative to sporulation. The role of sigma B in related Gram-positive bacteria (including cyanobacteria) with special emphasis on pathogenic bacteria is discussed.

Bacillus subtilis↗
PubMed1985

Response of general practitioners to a national dental office evaluation program. Office of Quality Assurance.

The methods used and the results achieved in an effort to solicit 300 volunteers to test the feasibility of a dental office assessment instrument have been described. In response to personal letters to general practitioners in 14 states, 13.9% returned a card indicating a willingness to consider participation. The response rate from different states ranged from 8% to 21.7% with the response being more favorable from states with fewer dentists. Year of graduation from dental school had little effect on the rate of response. Rural dentists responded at a slightly more favorable rate. Of dentists responding, 71% did so within 2 weeks and 90% within the first month after receiving the solicitation. Mail solicitation can be used successfully in recruiting private practitioners for participation in an in-office practice assessment program.

Adult↗
PubMed2003

The yeast Pdr15p ATP-binding cassette (ABC) protein is a general stress response factor implicated in cellular detoxification.

ATP-binding cassette (ABC) transporters play important roles in drug efflux, but some may also function in cellular detoxification. The Pdr15p ABC protein is the closest homologue of the multidrug efflux transporter Pdr5p, which mediates pleiotropic drug resistance to hundreds of unrelated compounds. In this study, we show that the plasma membrane protein Pdr15p displays limited drug transport capacity, mediating chloramphenicol and detergent tolerance. Interestingly, Pdr15p becomes most abundant when cells exit the exponential growth phase, whereas its closest homologue, Pdr5p, disappears after exponential growth. Furthermore, in contrast to Pdr5p, Pdr15p is strongly induced by various stress conditions including heat shock, low pH, weak acids, or high osmolarity. PDR15 induction bypasses the Pdr1p/Pdr3p regulators but requires the general stress regulator Msn2p, which directly decorates the stress response elements in the PDR15 promoter. Remarkably, however, Pdr15p induction bypasses upstream components of the high osmolarity glycerol (HOG) pathway including the Hog1p and Pbs2p kinases as well as the dedicated HOG cell surface sensors. Our data provide evidence for a novel upstream branch of the general stress response pathway activating Msn2p. In addition, the results demonstrate a cross-talk between stress response and the pleiotropic drug resistance network.

ATP-Binding Cassette Transporters↗
PubMed1999

[The 'Diabetes mellitus type 2' guideline (first revision) of the Dutch College of General Practitioners: response from family practice].

The first revision of the guidelines of the Dutch College of General Practitioners on diabetes mellitus type 2 has been prepared by experts from primary and secondary care. This might be a big improvement, since the guidelines will be welcomed by general practitioners as well as by specialists. One item that will cause debate is that the threshold to make the diagnosis of diabetes is decreased to 6.1 mmol/l. This will increase the number of diabetes patients and the GP's workload. Another controversy is made by the advice to screen for unknown diabetics in risk groups using case-finding. There are many questions about the feasibility of this advice while conclusive evidence that it will lead to better prognosis is not yet established.

Blood Glucose↗
PubMed2002

A phylogenomic study of the general stress response sigma factor sigmaB of Bacillus subtilis and its regulatory proteins.

Regulation of expression of the general stress regulon of Bacillus subtilis is mediated by the activation of the alternative sigma factor sigmaB. Activation of sigmaB is accomplished by a complex regulatory network involving protein-protein interactions and reversible protein phosphorylation. PSI-BLAST searches were performed and phylogenetic trees for sigmaB and its regulatory proteins were constructed. Occurrence of sigmaB is restricted to a small group of gram-positive bacteria (Bacillus, Staphylococcus, Listeria). Related sigma factors also involved in stress responses are present in Mycobacterium tuberculosis, Streptomyces species and even in cyanobacteria (Synechocystis species). Putative regulatory proteins found in several other bacterial species can be broadly catagorized into three categories: Anti sigma factors, anti-anti sigma factors and phosphatases. Anti sigma factors are able to bind to sigma factors and are also kinases of anti sigma factor antagonists. Only in their nonphosphorylated state, these antagonists are able to bind to the anti sigma factor. Phosphorylated antagonists can be dephosphorylated by PP2C phosphatases. These phosphatases are of pivotal importance for activation of the sigma factor. Different phosphatases identified in this search contain a wide variety of domains found in signal transducing proteins (PAS/PAC, GAF, REC, HATase_c, HAMP). The HATPase_c domain found in several phosphatases most probably constitutes a serine/threonine kinase domain of anti sigma factors. Such proteins are most probably bifunctional anti-anti sigma factor kinases and phosphatases. The regulatory network of anti-anti sigma factors anti sigma factors and phosphatases is probably ancient and most likely evolved from a structurally similar network found in the Deinococcus radiodurans genome. In completely sequenced genomes of several bacterial species, some elements of the network are missing. The N-terminus of RsbU, a phosphatase activated in response to environmental stress exhibits similarities to a region in the beta chain of phenylalanyl-tRNA synthetases.

Amino Acid Sequence↗
PubMed1986

Wh interrogative production in agrammatic aphasia: an experimental analysis of auditory-visual stimulation and direct-production treatment.

The effects of auditory-visual stimulation treatment derived from principles associated with a stimulation approach for aphasia treatment and direct-production treatment derived from a behavioral or learning approach were examined in 4 neurologically stable agrammatic aphasic subjects. Subjects were trained to produce selected exemplars of wh interrogative morphemes in complete sentence contexts, while the acquisition, response generalization (both within and across interrogative forms), stimulus generalization (to language samples), and maintenance effects of the two treatments were assessed. An alternating treatments design (ATD) in combination with a multiple-baseline design across behaviors and a multiple-baseline design across subjects was employed. Interrogative constructions were counterbalanced across subjects and treatments, and probes were administered daily to assess treatment effects. Results indicated that direct-production treatment was consistently more effective than auditory-visual stimulation treatment in facilitating acquisition of target responses for all subjects. Response generalization within interrogative forms paralleled acquisition regardless of treatment approach. Stimulus generalization to the elicited language-sample condition was not evident, however, trained responses were maintained subsequent to treatment. These data provided support for using direct-production treatment for interrogative intervention with agrammatic aphasic patients and indicated that training a selected number of exemplars of target interrogatives results in generalization of that question form to novel language responses. However, the lack of generalization across interrogatives indicated that wh interrogatives do not constitute a response class and, thus, pointed out a need for programming generalization to untrained members of that linguistic class and to spontaneous language.

Acoustic Stimulation↗
PubMed1998

Long-term follow-up of levodopa responsiveness in generalized dystonia.

OBJECTIVES: To assign an accurate diagnosis to patients with dystonia based on the presence of sustained levodopa responsiveness and to determine whether motor fluctuations occur in patients with dystonia who are withheld from levodopa. PATIENTS AND METHODS: Patients with generalized dystonia who responded to treatment in the 1970s with levodopa/carbidopa were surveyed by phone and then examined during a 3-day levodopa holiday. Functional imaging with fluorodopa positron emission tomography was performed on a subset of patients. RESULTS: In the phone interview, 4 of 7 patients with a diagnosis of dopa-responsive dystonia reported the wearing-off effect a short while (within 4-8 hours) after missing a dose of levodopa. Five patients with dopa-responsive dystonia were examined repetitively during levodopa withdrawal, and 3 developed recurrent symptoms of dystonia as the drug was withheld. In each case, worsening of dystonia did not occur until 29 hours or more after levodopa withdrawal, providing evidence for a response profile similar to the long duration response described in Parkinson disease. No significant changes were seen in the dystonia scores of the 3 patients with idiopathic torsion dystonia who were withheld from levodopa. CONCLUSIONS: We suggest that the subjective feeling of wearing off experienced by our patients with dopa-responsive dystonia may have been for one of the nonmotor effects of levodopa, such as mood elevation. Our data provide objective evidence for the often-repeated assertion that motor fluctuations (analogous to those in levodopa-treated patients with Parkinson disease) do not occur in patients with dopa-responsive dystonia.

Antiparkinson Agents↗
PubMed2000

Induction of the multixenobiotic defense mechanism (MXR), P-glycoprotein, in the mussel Mytilus californianus as a general cellular response to environmental stresses.

A multixenobiotic resistance mechanism (MXR) related to the P-glycoprotein multidrug transporter protein (p-gp) has been identified and characterized in several marine invertebrates. p-gp activity and protein titer is induced by exposure to toxins, supporting the suggestion that the role for this transporter is protection from xenobiotics by reducing accumulation of toxins in cells. In this study, we report on the specificity of the induction of the transporter by various chemical and physical stressors. p-gp substrates (including the pesticides pentachlorophenol and chlorthal) as well as non-substrates (including DDE and sodium arsenite) induced p-gp activity and protein titer in the gill tissues of the mussel Mytilus californianus. Similarly, mussels exposed to heat shock of 20 degrees C or 25 degrees C exhibited increased p-gp titer and activity compared to mussels held at ambient (12 degrees C) temperature seawater. Some of the same treatments that induced an increase in p-gp caused a concomitant increase in hsp70, but hsp induction was not always associated with induction of the p-gp protein. These findings suggest that p-gp induction in mussels may be part of a general cellular stress response. This response, however, does not appear to be always coupled with the hsp70 response in mussels.

Journal Article↗
PubMed1978

Aerosolized antigen dose-response studies in asthmatic monkeys.

This study used rhesus monkeys which had consistent respiratory responses to a standard (single dose) aerosolized concentration of A. Beginning at lower concentrations of A which did not produce an airway response, fourfold increases in concentrations of A were aerosolized until an airway response occurred. Compared with the single-dose SAC after the TAC, some consistently reactive animals did not respond to the SAC, the maximal concentration of A used for testing. Thus the TAC may result in an acute form of airway desensitization. Animals vary in the threshold concentrations of A required to produce an airway response. A repeat challenge with the threshold antigen concentration during the same experiment resulted in a second response generally greater than the initial response at the same concentration. When the SAC system was similarly evaluated by repeat challenges with the same A concentration, the second response was generally less than the first. Different methods for evaluation of pharmacologic inhibitors of IgE-mediated airway responses may be developed from this rhesus model of asthma.

Aerosols↗
PubMed2002

[The practice guideline 'Refraction errors' from the Dutch College of General Practitioners: response from the perspective of ophthalmology].

The practice guideline 'Refraction errors' from the Dutch College of General Practitioners provides a guideline for referral of persons aged 6 to 65 with gradual loss of vision to either an optician or an ophthalmologist. In this guideline, relevant questions regarding important symptoms are missing, and the value of the proposed examination employing 'diagnostic refraction' has insufficient scientific support. In addition, the possibility to send children between 6 and 10 years of age to the optician may be dangerous for some of the patients, and there are no explicit indications for the urgency of referral to the ophthalmologist. Due to these short-comings, the guideline may fail to provide optimal preventive and therapeutic eye care for the target group of patients concerned.

Adolescent↗
PubMed2005

[The practice guideline 'CVA' from the Dutch College of General Practitioners; a response from the perspective of general practice].

The practice guideline from the Dutch College of General Practitioners regarding the diagnosis, treatment and follow-up of a patient with a cerebrovascular accident recommends the patient's referral to a so-called 'stroke-unit'. Thrombolysis within 3 hours after the onset of a stroke should be reconsidered, although its effectiveness remains disputable. The guideline does not explicitly address the GP's responsibility for secondary prevention. The role of the GP in the process of rehabilitation and follow-up in the years after the CVA is described in detail. In so doing, this phase gets the attention it deserves.

Humans↗
PubMed1989

Temperature dependence of in vitro pituitary, testis, and thyroid secretion in a turtle, Pseudemys scripta.

In vitro culture was used to examine the direct actions of temperature at the level of pituitary hormone [luteinizing hormone (LH), thyrotropin (TSH), growth hormone (GH), prolactin (PRL)] responses to neuropeptides and two related peripheral endocrine responses [thyroid hormone (T4) and testicular androgen secretion] to pituitary hormones (TSH and gonadotropins) in a turtle, Pseudemys scripta. All these responses were fully suppressed at very low temperatures (5-6 degrees) and maximal near the species' preferred body temperature (28 degrees), but sensitivities differed markedly in intermediate ranges. At the pituitary level, the response of TSH, GH, and PRL to thyrotropin-releasing hormone (TRH) was considerably more temperature sensitive than the response of LH to gonadotropin-releasing hormone (GnRH) stimulation. TSH, GH, and PRL were unresponsive at 20 degrees or below, whereas LH secretion was stimulated almost equally between 12 and 28 degrees; the main effect of cooling on LH secretion was to reduce the duration of the response to GnRH. There was no clear effect of previous thermal history on temperature sensitivity of pituitary neuropeptide responsiveness although the general responsiveness of the gland was altered; however, these latter effects may also be related to variations in other factors such as photoperiod, season, and nutrition. Temperature sensitivities of the thyroid and testes also differed, but in the opposite way from the related pituitary cell types. Thyroid glands were relatively insensitive to temperature and responded to TSH between 12 and 32 degrees, with no difference between 20 and 28 degrees. In contrast, testicular androgen secretion showed an abrupt decline in gonadotropin responsiveness below 28 degrees; dose sensitivity, response rate, and maximal output were affected. Results were similar for sea turtle LH, snapping turtle LH, and ovine follicle-stimulating hormone. Thus, the temperature dependence of the two endocrine systems may have a different rate-limiting component.

Androgens↗